The chromatin of eukaryotes consists of sets of eight histone molecules surrounded by DNA, forming beadlike units connected in a linear array. The possible significance of the histones for gene regulation depends on the relation of the beads to base sequences in the DNA. A specific relation, which could result in particular sequences being exposed and others excluded from recognition by activator and repressor molecules, can be distinguished from the random case in a variety of ways. One approach is applicable to any DNA sequence for which the corresponding RNA molecule (mRNA, rRNA, tRNA) may be obtained. This approach can be used not only for detecting a specific relation of beads to base sequences in chromatin but also for determining whether the relation varies from one tissue to another or from normal to transformed cells, and whether the relation changes during oncogenesis or in the course of development. A similar procedure can be used to detect and isolate the proteins or other factors involved in establishing a specific relation of beads to base sequences during chromatin replication and assembly. A closely related question is whether the coiling of DNA around the bead results in regions of the DNA being exposed to particular advantage for recognition by base sequence-specific proteins or other molecules. The pattern of coiling of the DNA in a bead and also the supercoiling of linear arrays of beads will be investigated by X-ray diffraction analysis of solutions of beads, chains of beads, and if possible, crystals or paracrystalline material.